Yiu Chin Hang, Menzies Alexander M, Lu Christine Y
The University of Sydney School of Pharmacy, Camperdown, NSW, Australia.
Faculty of Medicine and Health, Kolling Institute, The University of Sydney and the Northern Sydney Local Health District, Sydney, NSW, Australia.
Target Oncol. 2025 Jun 30. doi: 10.1007/s11523-025-01164-2.
Immune checkpoint inhibitors are standard treatment for advanced melanoma. Pembrolizumab (programmed cell death-1 inhibitor) monotherapy is recommended as first-line treatment. However, real-world evidence on its efficacy and safety in Australia, a region with the highest melanoma incidence, remains limited.
This study aimed to assess real-world outcomes of pembrolizumab in patients with advanced melanoma in Australia.
A retrospective cohort study was conducted using national Pharmaceutical Benefits Scheme and National Death Index data via the Australian Bureau of Statistics DataLab. Patients who initiated pembrolizumab monotherapy for stage III/IV unresectable melanoma (1 January, 2017-30 June, 2022) were included. Kaplan-Meier analyses and multivariate Cox regressions were performed to assess overall survival and time to treatment discontinuation. Immune-related adverse events were inferred from corticosteroid and levothyroxine prescriptions. Subgroup analyses were performed by age (18-64, 65-84, ≥ 85 years) and sex.
Among 4127 patients, the median overall survival was 816 days. Mortality was higher in patients aged 65-84 years (adjusted hazards ratio 1.39, 95% confidence interval 1.24-1.56) and ≥85 years (adjusted hazards ratio 1.93, 95% confidence interval 1.69-2.21) versus 18-64 years. Median time to treatment discontinuation was 377 days, with a higher discontinuation rate in female individuals (adjusted hazards ratio 1.19, 95% confidence interval 1.09-1.29). Incident corticosteroid and levothyroxine prescriptions were observed in 19.3 and 7.6% of patients, respectively.
Our findings align with clinical trials, demonstrating similar survival outcomes. Younger patients benefited more from pembrolizumab, while female individuals had shorter treatment durations. Further research is required to explore immune checkpoint inhibitor efficacy, safety, and treatment disparities.
免疫检查点抑制剂是晚期黑色素瘤的标准治疗方法。帕博利珠单抗（程序性细胞死亡蛋白1抑制剂）单药治疗被推荐作为一线治疗方案。然而，在黑色素瘤发病率最高的地区澳大利亚，关于其疗效和安全性的真实世界证据仍然有限。
本研究旨在评估帕博利珠单抗在澳大利亚晚期黑色素瘤患者中的真实世界疗效。
通过澳大利亚统计局数据实验室，利用国家药品福利计划和国家死亡指数数据进行了一项回顾性队列研究。纳入了2017年1月1日至2022年6月30日开始接受帕博利珠单抗单药治疗III/IV期不可切除黑色素瘤的患者。进行了Kaplan-Meier分析和多变量Cox回归，以评估总生存期和治疗中断时间。通过皮质类固醇和左甲状腺素处方推断免疫相关不良事件。按年龄（18 - 64岁、65 - 84岁、≥85岁）和性别进行亚组分析。
在4127例患者中，中位总生存期为816天。65 - 84岁患者（调整后风险比1.39，95%置信区间1.24 - 1.56）和≥85岁患者（调整后风险比1.93，95%置信区间1.69 - 2.21）的死亡率高于18 - 64岁患者。中位治疗中断时间为377天，女性患者的中断率更高（调整后风险比1.19，95%置信区间1.09 - 1.29）。分别有19.3%和7.6%的患者出现皮质类固醇和左甲状腺素处方。
我们的研究结果与临床试验一致，显示出相似的生存结果。年轻患者从帕博利珠单抗中获益更多，而女性患者的治疗持续时间较短。需要进一步研究以探索免疫检查点抑制剂的疗效、安全性和治疗差异。
